A successful vaccine against intracellular pathogens will not only stimulate the humoral immune response via the Major Histocompatibility Complex (MHC) class II pathway, but (more importantly) will also induce destruction of infected cells through activation of the MHC class I pathway. The latter response is achieved through cytosolic degradation of foreign protein in infected cells, such that fragments of the foreign material are shuttled to the cell surface for presentation to CD8+ cytotoxic T cells (CTL). Failure to activate the MHC class I pathway is a common deficiency of vaccines based on purified recombinant antigens.
Heat shock proteins (“Hsps”) are a family of molecular chaperone proteins produced by prokaryotic and eukaryotic cells, and which play essential roles in a multitude of intra- and intercellular processes, in particular in antigen processing and presentation of antigen fragments to the MHC I system at the cell surface. Fusion proteins of certain hsp proteins with other peptides have been successfully used in vivo to elicit a CTL response specific to those peptides.
Furthermore, hsps are now known to be targets of anti-pathogen Immune responses against a multitude of bacterial, fungal, helmintic and protozoan diseases. Immunization of mammals with a variety of different pathogen hsps (principally of mycobacterial origin) induces strong immune responses and provides protection against diseases caused by these pathogens. The strength of mammalian immune responses to pathogenic hsps is speculated to be due in part to the existence of multiple B cell and T cell epitopes on these proteins.
A live, non-virulent strain of Arthrobacter (a member of the family of Corynebacteria) is marketed as a vaccine intended to protect salmon and other farmed fish against bacterial kidney disease (BKD). The characteristics of this strain are disclosed in WO 98/33884. This vaccine is unique in that it is the first live culture to have been licensed for use in aquaculture.
Surprisingly, it has now been shown that Arthrobacter hsp70 can be effectively employed in vaccines against varied fish pathogens.